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  • The EMBO Journal (2002) 21, 2655 - 2663
  • doi:10.1093/emboj/21.11.2655

The oxidoreductase ERp57 efficiently reduces partially folded in preference to fully folded MHC class I molecules

Antony N. Antoniou1, Stuart Ford1, Magnus Alphey1, Andrew Osborne1, Tim Elliott2 and Simon J. Powis1

  1. Division of Cell Biology and Immunology, School of Life Sciences, University of Dundee, Dundee DD1 5EH
  2. Cancer Sciences Division, University of Southampton School of Medicine, Southampton General Hospital, Southampton SO16 6YD, UK

Correspondence to:

Simon J. Powis, E-mail: s.j.powis@dundee.ac.uk

Received 7 February 2002; Accepted 2 April 2002; Revised 2 April 2002

The oxidoreductase ERp57 is an integral component of the peptide loading complex of major histocompatibility complex (MHC) class I molecules, formed during their chaperone-assisted assembly in the endoplasmic reticulum. Misfolded MHC class I molecules or those denied suitable peptides are retrotranslocated and degraded in the cytosol. The presence of ERp57 during class I assembly suggests it may be involved in the reduction of intrachain disulfides prior to retrotranslocation. We have studied the ability of ERp57 to reduce MHC class I molecules in vitro. Recombinant ERp57 specifically reduced partially folded MHC class I molecules, whereas it had little or no effect on folded and peptide-loaded MHC class I molecules. Reductase activity was associated with cysteines at positions 56 and 405 of ERp57, the N-terminal residues of the active CXXC motifs. Our data suggest that the reductase activity of ERp57 may be involved during the unfolding of MHC class I molecules, leading to targeting for degradation.

  • Keywords:

    • chaperone,
    • endoplasmic reticulum,
    • MHC class I,
    • oxidoreductase ERp57,
    • protein folding